What is CAR-T cell persistence?

What is CAR T cell persistence? One of the issues with CAR T cell therapy is that you infuse the CAR T cells and then you sort of leave them alone and we know that they expand after you give them. They proliferate in the blood and they reach their peak at slightly different times. Abecma, which has been approved, reaches its peak earlier on than the Cilta cell, for which the data has been published in the Lancet earlier this year, where you see a peak in proliferation or an expansion at about three weeks or one month after infusion. So a little bit later than the Abecma. Another important question is the persistence of CAR T cells because over time there's a tendency of concentrations of these T cells in the blood to diminish. And so in most patients it becomes much harder or impossible to detect them after a couple months. Importantly, it is not fully understood and as CAR T becomes publicly available also earlier on, it's an important thing to study whether or not this persistence correlates to the duration of response. Because a naive interpretation could be to say that when we cannot detect a CAR T, it's not effective anymore. But I think it's slightly more complicated because we expect a CAR T to have their effect where the tumor is growing in the bone marrow and not necessarily in the peripheral blood. So it's possible that there's very low levels of the CAR T cells actually persisting in the bone marrow niche where the tumor is kept under control, even though it's no longer detectable in the blood. I also have to add that there's a very large variability in the persistence in the sense that there are some patients in which we see high levels of CAR T cells persist up to three, six months and longer, whereas in I would say most patients we see lower or undetectable levels after a couple months or a couple months after the infusion.